The objective of the proposed research is to prepare a series of sensitive and specific substrates for assaying blood proteases such as Factors VIIa, IXa, Xa, XIa, XIIa, plasmin, thrombin, kallikrein and the plasminogen activator. These proteins are the basis of important physiological processes such as blood clotting, fibrinolysis, the complement system and kinin release. Mapping of the extent of the extended substrate binding region in these proteases will be undertaken with synthetic substrates. The proposed research will attempt to determine the reasons for the high degree of substrate specificity of plasma proteases. The synthetic substrates also will be used to study how other plasma components such as phospholipids modulate the activity of these enzymes. The proposed research may lead to new methods for disease detection or to new mechanisms for the control or modulation of plasma protease activity in various disorders.